Angiotensin-converting enzyme inhibitors. 2. Perhydroazepin-2-one derivatives

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Abstract
.alpha.-[(3S)-3[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhyroazepin-1-yl]acetic acids (monoester monoacids) and their decarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituents at the 6-position showed a longer duration of action than one have the substituents at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.